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Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
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Single cell sequencing unraveling genetic basis of severe COVID19 in obesity

Antoine Fakhry AbdelMassih1,2, Raghda Fouda3,4, Aya Kamel5

  • 1Pediatric Cardiology Unit, Pediatrics' Department, Faculty of Medicine, Cairo University, Egypt.

Obesity Medicine
|September 30, 2020
PubMed

Insights

Single cell sequencing reveals COVID-19 risks in obese patients by linking immune responses and genetic factors. This approach aids in identifying high-risk individuals for precision medicine and suggests leptin sensitizers for effective anti-inflammatory therapy.

Area of Science:

  • Immunology
  • Genetics
  • Virology

Background:

  • COVID-19 severity varies across demographic groups, disproportionately affecting obese individuals, males, older adults, and Black populations.
  • Previous understanding linked COVID-19 severity primarily to ACE2 levels, but new research explores deeper cellular and genetic mechanisms.
  • Obesity shares common immune and genetic pathways with severe COVID-19, explaining increased risk.

Purpose of the Study:

  • To investigate the cellular and genetic mechanisms underlying COVID-19 severity, particularly in obese patients.
  • To identify novel therapeutic targets for managing severe COVID-19 outcomes.
  • To highlight the utility of single cell sequencing in precision medicine for infectious diseases.

Main Methods:

  • Utilized single cell sequencing to analyze cellular and genetic profiles in COVID-19 infection.
  • Compared immune and genetic responses in obese patients with severe COVID-19 to other demographic groups.
  • Examined the role of cell polarity, Furin protease, and ACE2 co-expression in viral entry and pathogenesis.

Main Results:

  • Identified shared mechanisms between obesity and severe COVID-19, including macrophage phenotype switching, altered gene expression, cytokine dysregulation (pro-inflammatory cytokine overexpression, regulatory cytokine depletion), T cell proliferation, and exhaustion.
  • Demonstrated that Furin protease co-expression with ACE2 plays a role in viral genesis.
  • Highlighted the potential of leptin sensitizers as a therapeutic strategy to modulate the immune response from Type 1 to Type 2.

Conclusions:

  • Single cell sequencing is crucial for rapid identification and treatment of patients at high risk for severe COVID-19, enabling precision medicine.
  • Immune modulators like leptin sensitizers show promise for treating COVID-19 by rebalancing the immune response, shifting from harmful inflammation to a beneficial state.
  • The study provides a more accurate explanation for increased COVID-19 risk and poor outcomes in obese individuals through shared genetic and immune pathways.

Keywords:
Beneficial inflammationCOVID-19Deleterious inflammationImmunologic switchObesityShared immunogeneticsSingle cell sequencing

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